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Geron Corporation (NASDAQ:GERN)

Update on Imetelstat Conference Call

March 12, 2014 08:30 AM ET

Executives

Anna Krassowska – Director-Investor Relations

John A. Scarlett – President and Chief Executive Officer

Analysts

Cory W. Kasimov – JPMorgan Securities, LLC

Brian J. Klein – Stifel, Nicolaus & Co., Inc.

Roy Buchanan – Piper Jaffray & Co

Graig Suvannavejh – MLV & Co. LLC

David Miller – Alpine BioVentures

Operator

Good day ladies and gentlemen and welcome to the Geron update on Imetelstat Conference Call. My name is Tracy and I will be your operator for today. At this time, all parties are on a listen-only mode. We will conduct a question-and-answer session towards the end of the conference. (Operator Instructions) As a reminder, this call may be recorded for training purposes. I would like to turn the call over to Anna Krassowska, Head of Investor Relations. Please go ahead ma'am.

Anna Krassowska

Thank you, Tracy. Good morning, everyone and thank you for joining us. With me today is John Scarlett, our President and Chief Executive Officer and Olivia Bloom, our Executive Vice President of Finance and Chief Financial Officer.

This morning, we issued a press release that announced that Imetelstat was placed on Clinical Hold. This release can be found on our website at www.geron.com. Today's call is also being webcast live on our website and will be available for replay through April 12.

Before we begin, please note that except for statements of historical facts, the statements during this conference call are forward-looking statements under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These include, without limitations, statements regarding the timelines, prospects and plans for Imetelstat, including anticipated timelines for clinical study initiation, clinical results and data, the therapeutic potential and safety of Imetelstat, and financial or operational projections or requirements including spending guidance.

These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Additional information concerning factors that could cause actual results to differ materially from those in the forward-looking statements is contained in Geron's periodic reports filed with the Securities and Exchange Commission under the heading Risk Factors, including Exhibit 99.1 of Geron’s current report on Form 8-K filed on January 30, 2014.

Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made and the facts and assumptions underlying the forward-looking statements may change, except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances.

I will now turn the call over to Chip to discuss to this mornings press release. Chip?

John A. Scarlett

Thanks Anna and good morning everyone and thank you for dialing into our call. Yesterday afternoon, we received verbal notification from the FDA that our IND for Imetelstat has been placed on full Clinical Hold. Although we’ve not yet received formal written notice from the FDA, we issued the press release this morning to facilitate prompt public disclosure in this event.

We’re surprised by these actions as we reported publicly in March 2013, we have observed persistent LFT abnormalities in the ET trial. At least one abnormal LFT has been observed in all of the patients in this trial. The majority were Grade 1 or Grade 2 elevations in ALT or AST. Reversible Grade 2 to Grade 3 elevations in ALT with Grade 1 or Grade 2 elevations in AST were observed within a few weeks of starting Imetelstat in some patients.

These latter abnormalities resolved with dose holds and dose reductions and did not recur with ongoing Imetelstat treatment. However, with longer dosing Grade 1 increases in alkaline phosphatase were observed associated with mostly Grade 1 and in some cases with Grade 2 unconjugated hyperbilirubinemia.

Since then we engaged an expert panel of liver experts who along with our internal safety staff, have periodically reviewed the data and all possible liver-related SAEs. Our and their conclusions were that the benefit risk profile with Imetelstat was favorable. These conclusions remained consistent as the ET trial progressed. FDA have now asked us to provide data regarding reversibility of these LFT abnormalities after patients have discontinued from Imetelstat in our own IND trials and to provide information regarding the incidence of, and if relevant reversibility of such abnormalities from other non-Geron sponsored studies including the Mayo Clinic IST. We will be working in the coming weeks to provide these data to FDA.

So with that operator let’s open the call to questions please.

Question-and-Answer Session

Operator

Thank you. (Operator Instructions) The first question comes from the line of Cory Kasimov from JPMorgan.

Cory W. Kasimov – JPMorgan Securities, LLC

Hey good morning guys, it’s Cory Kasimov from JPMorgan. Thanks for taking my questions. I guess first of all, just if you can put any sort of context around the term persistency, how long do these affects continue for and what's the longest you've seen this go out at this point?

John A. Scarlett

We’ve seen these Grade 1 increases in alkaline phosphatase and some of the hyperbilirubinemia persist as long as patients have been on the study. So in a couple of cases these have gone upwards of 20 plus months.

Cory W. Kasimov – JPMorgan Securities, LLC

Okay, and then last with the data you referenced last Spring I believe it was presented at EHA where the Grade 3 cases were deemed reversible. When they're reversible, do they just go to a lower grade and stay there or reversible means that those particular patients, they resolved completely?

John A. Scarlett

Yes, the reversible Grade 2 to Grade 3 elevations in the ALT in the ALT, which were sometimes associated with Grade 1 to Grade 2 elevations in AST resolved with dose holds and dose reductions and did not recur. So the focus today is on the persistent low grade LFT abnormalities, not those acute changes.

Cory W. Kasimov – JPMorgan Securities, LLC

Okay. And then my final question and I can hop back in the queue, is when you – when do you expect to receive the written communication from the FDA, did they let you know that? And is there any precedence or standard window the agency has to meet with you to discuss these types of matters?

John A. Scarlett

Generally what happens is that they inform today the current experiences are that they inform you, then they send a letter and you assimilate that, try to address information concerns and then get back to them. We would anticipate receiving that letter sometime quite soon and then formulating – looking for data and formulating a response.

Cory W. Kasimov – JPMorgan Securities, LLC

Okay. I appreciate you taking the questions.

John A. Scarlett

Sure.

Operator

Your next question comes from the line of Brian Klein from Stifel. Please go ahead.

Brian J. Klein – Stifel, Nicolaus & Co., Inc.

Hi, thanks, it's Brian Klein from Stifel. First, just wondering if you've seen these types of LFT abnormalities in other studies of Imetelstat, specifically in the non-small cell lung cancer or in the breast cancer studies?

John A. Scarlett

Yes as we have reported previously when we reviewed beginning roughly a year ago and we subsequently reported publicly in our review of data from the other non-ET Imetelstat studies conducted under our IND Brian, which were primarily as you said solid tumor studies. We did find similar patterns that where observed in ET study, but with a varying and generally lower frequency, and as was the case obviously previously no cases of [indiscernible] were observed and new safety signals have emerged. This is what we reported at that point.

Brian J. Klein – Stifel, Nicolaus & Co., Inc.

Okay, thanks. Also if you look back at your pre clinical studies, did you see these findings as well and were they reversible in those animals?

John A. Scarlett

Understood. We did not see any of these specific findings in the long-term chronic safety studies, preclinical safety studies. There were some changes in those studies consistent with class effects of oligonucleotides including some what were presumed to be somewhat inflammatory type reactions, but they are pretty non-specific and we will look again for evidence of reversibility of those effects, but it’s not 100% clear that the effects that we are seeing pre-clinically really, we do not know the relationship to those effects and what we’ve observed clinically.

Brian J. Klein – Stifel, Nicolaus & Co., Inc.

Okay, thank you. Going back to these patients in the ongoing IND studies, have you noted any clinical manifestations of these elevated LFTs? And has that been a concern to the prescribing physicians?

John A. Scarlett

We have not observed in general, Brian we have not observed any obvious worsening of cases as time has progressed or worsening of incidents. That's why as I commented earlier, we did not feel that the benefit risk assessment of the drug had really changed and as you may know when you have these really low level, but persistent abnormalities, it’s quite challenging to understand whether there really are any clinical sequelae associated with them unlike acute liver injury, where it is temporarily associated with something.

So I think certainly up to this point in time, we were not aware of any obvious clinical sequelae, but that’s part of the assessment that of course we’ll have to do now that we are on Clinical Hold in a more detailed manner.

Brian J. Klein – Stifel, Nicolaus & Co., Inc.

Great, thank you for taking my questions.

Operator

Your next question comes from the line of Charles Duncan from Piper Jaffray. Please go ahead.

Roy Buchanan – Piper Jaffray & Co

Hi, guys, it's Roy in for Charles. Thanks for taking the question, most have been answered. I guess I don't know if you guys could maybe indicate if there's any precedent drugs that you're aware of either in your experience or otherwise that the FDA has dealt with this issue and how that was resolved? Thanks.

John A. Scarlett

That’s a very good question. As we’ve discussed these findings over the past year with our own expert panel, the commentary has been that the vast majority of cases in which drugs have been implicated and actions needed to be taken with precedent drugs or precedent situations have always been acute liver injury. I cannot quote to you today a drug that has had very low grade persistent LFTs and that – in which, if this risk needed to be adjudicated. It doesn’t mean that there haven’t been, we’re just not aware of any, at least that come to mind initially. So I think that’s again part of the assessment that we have to do and report back and have a discussion with regulatory authorities about.

Roy Buchanan – Piper Jaffray & Co

Okay.

Operator

Your next question comes from the line of Graig from MLV & Co.

Graig Suvannavejh – MLV & Co. LLC

Hi, great, thanks. It’s Graig Suvannavejh from MLV. First of all, sorry to hear the news. My questions really have to do with the current MF study that Dr. Tefferi is running. Do you have any information on what liver enzymes look like from that study? And just taking a quick look at clinicaltrials.gov, it indicates that the study was to have completed in January of this year. So I'm wondering if you have any sense of when "final data" might be available from that study?

John A. Scarlett

So let’s take that in reverse order, Graig.

Graig Suvannavejh – MLV & Co. LLC

Sure.

John A. Scarlett

So first of all, you’re correct that the study was – enrollment was stopped in January of this year. I’d like to say that, that decision had nothing to do with liver function test abnormalities. That was never discussed and we are unaware of any reason vis-à-vis liver abnormalities that played any role in stopping the study. The data from that study we expect to be submitted to ASH this year and so I think that people will get an opportunity to see that at that point in time.

We do not have a great deal of insight into the specifics of the LFT – of any LFT abnormalities in Dr. Tefferi’s study. And I think what we should do is simply state that it’s one of the goals of our evaluation to gain much better insight into that. I would just comment, as you may know, that – well, maybe I’ll just stop there and take the next question.

Graig Suvannavejh – MLV & Co.

Sure. Just as a follow-up, do you know, well you probably do, the doses at which these LFTs were seen in the PV trial and how – can you remind us how that compares with the doses that were evaluated in Dr. Tefferi’s trial?

John A. Scarlett

So the ET and PV patients were generally treated with 9.4 milligrams per kilogram every week at least until the patients had achieved complete remission, hematologic remission. And then in some of the going out later in the study, some of these patients continued to receive in general 9.4 milligrams per kilo, but at varying intensities let’s to say every q.3 weeks to six weeks.

And in Dr. Tefferi's study, I can say that in general, I would guess that an average dose is probably around 9.4, q.3, but of course now as particularly as we've reported previously, patients who had CR have been receiving lower and lower doses in particular some have been reduced to 7.5 milligrams per kilo and being given now every six weeks for the CR patients. So it's a little hard for me to be more than just general.

I think this is part of our analysis going forward in a more detailed manner, but I would say that because of the myelosuppression that has been observed in the MF studies and in which there was certainly substantially less myelosuppression observed in the ET study, doses on the whole have been lower in the long-term treatment of the MF patients, but again compared to the ET study. However, I think we really should all wait and let us do the analysis of that and give you much more detailed data.

Graig Suvannavejh – MLV & Co. LLC

Okay, thank you. And one last question and then maybe I'll jump back in the queue. I know it's very early days and it's maybe difficult for to you speculate, but any sense on how this impacts how you think about timing on a go-forward basis? I know the sponsored study was supposed to start in the first half. And given what you know about industry and FDA, is there any way to put into some framework how you're thinking about what this might do in terms of going forward with Imetelstat and MF?

John A. Scarlett

Well, I think that we have stated this morning in our press release and I would reiterate it that the Company's planned Phase 2 clinical trial in myelofibrosis is likely to be delayed due to this Clinical Hold. So I think beyond that speculation is not warranted. Remember, we haven’t even received the letter from FDA, so this is our guess today, but I think we'll have more to say about it as we understand more.

Graig Suvannavejh – MLV & Co. LLC

Okay.

Operator

Your next question comes from the line of David Miller, Alpine BioVentures. Please go ahead.

David Miller – Alpine BioVentures

Hi, good morning and thanks for taking my question. Have any patients failed to resolve to zero on their LFTs with dose withdrawal?

John A. Scarlett

So what we reported previously and as far as I know is the case, was that the patients with the acute elevations of AST and ALT when dose reduced, did have resolution and it’s not recurred. I do not have insight into every single patient, so I really have to qualify that as a general statement. However, there is certainly many patients, and this is really the source of this whole discussion, there are many patients who have had dose reductions or dose modifications for a variety of reasons who have had these persistent low grade LFTs.

The question at hand that we don't have the complete information and data on today is what happens when patients dose reduce if you will to zero meaning that they come off of the drug. That's one of the things that we are in the process of evaluating and finding out. That's really the reversibility question. So we don’t really have an answer to that question today. And that's what we need to go do more work on.

David Miller – Alpine BioVentures

Okay. And because presuming that with patients come off the drug, they're going to be off these various trials. How difficult do you think it will be to acquire those data as far as – hey, the patient's off the trial. How are you going to go about finding out what their LFTs are?

John A. Scarlett

So that's obviously a very relevant comment. And it can be quite difficult to go back and obtain such data. We will make every effort to do that. In some cases it may require we consenting patients to look at their data that has occurred over the usual space of time that is covered by most protocols which has come off of drug. The original plan was to provide information in that regard. So it will certainly be challenging. Some patients remain in similar medical care treatment systems may be easier to follow. But I think it is a challenge and we will – all can say right now is we will do our best to do so and we will know more after we start that process.

David Miller – Alpine BioVentures

Okay. And then the last question is, is that in the cases of – where you have the more information on the higher grades, how long after either dose reduction or dose withdrawal did those patients have their levels return to zero?

John A. Scarlett

I don't know the exact answer to that. I haven't looked at that data for some time. But it was fairly rapid and it appeared to be unquestionably temporally related to the dose reduction of dose hold and…

David Miller – Alpine BioVentures

So is it like on the order of weeks or months?

John A. Scarlett

Yes, it’s weeks.

David Miller – Alpine BioVentures

Okay.

John A. Scarlett

As far as I know, it was weeks or certainly not a long period of time. So as I said again, our perception today, absent further information, is that this is really about the low grade, the persistent low grade LFT abnormalities and not these acute abnormalities.

David Miller – Alpine BioVentures

Understood, understood. Thanks for taking my questions, I appreciate it.

John A. Scarlett

Sure.

Operator

Thank you. Ladies and gentlemen, that concludes your question-and-answer session. I would now like to turn the call over to Dr. John Scarlet, CEO, for closing remarks.

John A. Scarlett

Thanks everyone for your time today. We'll look forward to further discussions. I think that's the best way to leave it today. Thank you, Operator, we're done.

Operator

Thank you for your participation today. That concludes your presentation. You may now disconnect and have a good day.

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